Mechanism research on microRNA-669f-5p/deoxycytidylate deaminase axis mediating sevoflurane-induced cognitive dysfunction in aged mice.

OBJECTIVE: To investigate the role of the microRNA (miRNA)-669f-5p/deoxycytidylate deaminase (Dctd) axis in sevoflurane inducing cognitive dysfunction in aged mice. METHODS: Sixty-six C57BL/6J mice were used in the experiment model and were randomly divided into the sevoflurane group and the control group. The mice in the sevoflurane group were anesthetised with 3.4% sevoflurane, whereas those in the control group were air-treated for the same period. The study was then performed using bioinformatics sequencing, as well as in vitro and in vivo validation. RESULTS: The mice in the sevoflurane group showed significant cognitive impairments in terms of a decrease in both spatial learning and memory abilities. Experimental doses of miR-669f-5p agonist exhibited no obvious effect on cognitive function following sevoflurane inhalation, but inhibiting the expression of miR-669f-5p could alleviate the impairments. Based on the results of the bioinformatics sequencing, miR-669f-5p/Dctd and the toll-like receptor (TLR) signalling pathway could be the key miRNA, gene and pathway leading to postoperative cognitive dysfunction following sevoflurane inhalation. The aged mice showed significantly increased expression of miR-669f-5p in the hippocampus following sevoflurane inhalation, and upregulating/inhibiting its expression could increase/decrease TLR expression in the hippocampus. Furthermore, miR-669f-5p could reduce the expression of the Dctd gene by binding to its 3'untranslated region. CONCLUSION: The miR-669f-5p/Dctd axis plays an important role in sevoflurane inducing cognitive dysfunction in aged mice, providing a new direction for further development of therapeutic strategies concerning the prevention and treatment of cognitive dysfunction associated with sevoflurane anaesthesia.

Peripheral inflammation as a potential mechanism and preventive strategy for perioperative neurocognitive disorder under general anesthesia and surgery.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society's health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

Current status of sevoflurane anesthesia in association with microglia inflammation and neurodegenerative diseases.

Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti-inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.

Emerging Insights into Postoperative Neurocognitive Disorders: The Role of Signaling Across the Gut-Brain Axis.

The pathophysiological regulatory mechanisms in postoperative neurocognitive disorders (PNCDs) are intricately complex. Currently, the pathogenesis of PNCDs has not been fully elucidated. The mechanism involved may include a variety of factors, such as neuroinflammation, oxidative stress, and neuroendocrine dysregulation. Research into the gut microbiota-induced regulations on brain functions is increasingly becoming a focal point of exploration. Emerging evidence has shown that intestinal bacteria may play an essential role in maintaining the homeostasis of various physiological systems and regulating disease occurrence. Recent studies have confirmed the association of the gut-brain axis with central nervous system diseases. However, the regulatory effects of this axis in the pathogenesis of PNCDs remain unclear. Therefore, this paper intends to review the bidirectional signaling and mechanism of the gut-brain axis in PNCDs, summarize the latest research progress, and discuss the possible mechanism of intestinal bacteria affecting nervous system diseases. This review is aimed at providing a scientific reference for predicting the clinical risk of PNCD patients and identifying early diagnostic markers and prevention targets.

Research advances in the influence of lipid metabolism on cognitive impairment.

Cognitive impairment (CI) is a mental disorder related to cognition and understanding, which is mainly categorized into mild CI and senile dementia. This disease is associated with multiple factors, such as chronic brain injury, aging, chronic systemic disease, mental state, and psychological factors. However, the pathological mechanism of CI remains unclear; it is usually associated with such underlying diseases as diabetes and hyperlipidemia. It has been demonstrated that abundant lipid metabolism indexes in the human body are closely related to CI, including total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein, and so forth. As a crucial risk factor for CI, hyperlipidemia is of great significance in the occurrence and development of CI. However, the specific correlation between dyslipidemia and CI is still not fully elucidated. Besides, the efficacy of lipid-lowering drugs in the prophylaxis and treatment of CI has not been clarified. In this study, relevant advances in the influence of lipid metabolism disorders in CI will be reviewed, in an attempt to explore the effect of mediating blood lipid levels on the prophylaxis and treatment of CI, thus providing a reference for its clinical management.

Research progress on the association between MicroRNA and postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a significant complication following surgery. The precise mechanisms underlying POCD remain elusive, although it is speculated that they involve central nervous system inflammation, oxidative stress and cellular apoptosis. MicroRNAs (miRNAs), a class of non-coding RNAs widely distributed in eukaryotes, have been implicated in the pathogenesis of neurodegenerative disorders and could potentially impact POCD. This review explores the association between miRNAs and POCD and provides an overview of the progress of current research on miRNAs in the pathogenesis, diagnosis, and treatment of POCD.

Risk Factors for Postanesthetic Emergence Delirium in Adults: A Systematic Review and Meta-analysis.

Emergence delirium (ED) is delirium that occurs during or immediately after emergence from general anesthesia or sedation. Effective pharmacological treatments for ED are lacking, so preventive measures should be taken to minimize the risk of ED. However, the risk factors for ED in adults are unclear. In this systematic review and meta-analysis, we evaluated the evidence for risk factors for ED in adults. The PubMed, Scopus, Cochrane Library, Google Scholar, and Embase databases were searched for observational studies reporting the risk factors for ED in adults from inception to July 31, 2023. Twenty observational studies reporting 19,171 participants were included in this meta-analysis. Among the preoperative factors identified as risk factors for ED were age <40 or ≥65 years, male sex, smoking history, substance abuse, cognitive impairment, anxiety, and American Society of Anesthesiologists physical status score III or IV. Intraoperative risk factors for ED were the use of benzodiazepines, inhalational anesthetics, or etomidate, and surgical factors including abdominal surgery, frontal craniotomy (vs. other craniotomy approaches) for cerebral tumors, and the length of surgery. Postoperative risk factors were indwelling urinary catheters, the presence of a tracheal tube in the postanesthetic care unit or intensive care unit, the presence of a nasogastric tube, and pain. Knowledge of these risk factors may guide the implementation of stratified management and timely interventions for patients at high risk of ED. The majority of studies included in this review investigated only hyperactive ED and further research is required to determine risk factors for hypoactive and mixed ED types.

To re-examine the intersection of microglial activation and neuroinflammation in neurodegenerative diseases from the perspective of pyroptosis.

Neurodegenerative diseases (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and motor neuron disease, are diseases characterized by neuronal damage and dysfunction. NDs are considered to be a multifactorial disease with diverse etiologies (immune, inflammatory, aging, genetic, etc.) and complex pathophysiological processes. Previous studies have found that neuroinflammation and typical microglial activation are important mechanisms of NDs, leading to neurological dysfunction and disease progression. Pyroptosis is a new mode involved in this process. As a form of programmed cell death, pyroptosis is characterized by the expansion of cells until the cell membrane bursts, resulting in the release of cell contents that activates a strong inflammatory response that promotes NDs by accelerating neuronal dysfunction and abnormal microglial activation. In this case, abnormally activated microglia release various pro-inflammatory factors, leading to the occurrence of neuroinflammation and exacerbating both microglial and neuronal pyroptosis, thus forming a vicious cycle. The recognition of the association between pyroptosis and microglia activation, as well as neuroinflammation, is of significant importance in understanding the pathogenesis of NDs and providing new targets and strategies for their prevention and treatment.

Thrifty effect of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic effectiveness: A prospective, triple-blind, randomized controlled, polycentric clinical trial.

Aim: To investigate the thrifty effects of subanesthetic-dose S-ketamine on postoperative opioids and its safety and analgesic efficacy. Methods: Four-hundred and twenty patients were divided into the control group (CON group), the S-ketamine 0.2 mg/kg group (ES0.2 group), and the S-ketamine 0.3 mg/kg group (ES0.3 group) randomly. Major indicators include the Visual Analogue Scale (VAS), the times of compression with analgesic pumps after surgery, and analgesic drug consumption from anesthesia induction to 48 h after surgery. Minor records include vital signs, the use of vasoactive drugs, the Ramsay scores, the occurrence of adverse events including nervous system reaction, and the patient's satisfaction with anesthesia. Results: Compared with the CON group, VAS scores decreased in the ES0.2 and ES0.3 groups (p < 0.05). At 10 min after extubation, the VAS scores of the ES0.3 group were lower than that of the ES0.2 group (p < 0.05). The total number of compression with analgesic pumps of the ES0.3 group was lower than that of the CON group (p < 0.05). The opioid consumption after surgery of the ES0.3 group was lower than those of the CON group and the ES0.2 group (p < 0.05). The ES0.3 group's heart rate (HR) was faster but the use of vasoactive, drug consumption was less than the other two groups (p < 0.05). There were no significant differences in the incidence of postoperative adverse events and anesthetic satisfaction among the three groups. Conclusion: Subanesthetic-dose S-ketamine at 0.2-0.3 mg/kg especially the 0.3 mg/kg in general anesthesia induction can safely and effectively reduce postoperative pain and save postoperative opioid consumption.

The effective doses of remimazolam besylate in the procedural sedation of endoscopic retrograde cholangiopancreatography.

This study aimed to determine the values of the half-effective dose (ED50) and 95% effective dose (ED95) of remimazolam besylate used in the procedural sedation of endoscopic retrograde cholangiopancreatography (ERCP). Sixty patients who fulfilled the inclusion and exclusion criteria of this study were selected. Sufentanil was administered intravenously and remimazolam besylate was administered 2 min later. ERCP treatment was feasible when the modified alertness/sedation (MOAA/S) score was ≤2. If choking or movement occurred during duodenoscope placement, it was considered as a positive reaction. The dose was increased in the next patient; otherwise, it was considered as a negative reaction, and the dose was reduced in the next patient. The ED50 and ED95 values and 95% confidence interval (CI) of remimazolam besylate were calculated by Probit regression analysis. All 60 patients completed the trial. The ED50 and ED95 values of remimazolam besylate were 0.196 and 0.239 mg/kg, respectively, for the procedural sedation of ERCP. The time of MOAA/S score ≤ 2 was (82.58 ± 21.70) s, and the mean time of awakening was (9.03 ± 5.64) min. Transient hypotension was observed in two patients without medical intervention. The ED50 and ED95 values of remimazolam besylate used in the procedural sedation of ERCP were 0.196 and 0.239 mg/kg, and the dose of the medications has definite efficacy and good safety.

The role of TREM1 in regulating microglial polarization in sevoflurane-induced perioperative neurocognitive disorders.

Microglia-mediated neuroinflammatory responses play a key role in perioperative neurocognitive disorders (PND). Triggering receptor expressed on myeloid cells-1 (TREM1) has been shown to be a key regulator of inflammation. However, its role in PND remains largely unknown. This study aimed to evaluate the role of TREM1 in sevoflurane-induced PND. We applied AAV knockdown TREM1 in hippocampal microglia in aging mice. The mice were then subjected to neurobehavioral and biochemical testing after the intervention of sevoflurane. We found that sevoflurane inhalation can cause PND in mice, increase hippocampal TREM1 expression, polarize microglia to M1 type, upregulate TNF-α and IL-1ß expression (pro-inflammatory), and inhibit TGF-ß and IL-10 expression (anti-inflammatory). Knocking down TREM1 can improve sevoflurane-induced cognitive dysfunction, reduce M1 type marker iNOS, and increase M2 type marker ARG, improving the neuroinflammation. TREM1 is a target for sevoflurane-induced PND prevention.

Association of volatile anesthesia exposure and depth with emergence agitation and delirium in children: Prospective observational cohort study.

Background: Sevoflurane anesthesia is widely used in pediatric ambulatory surgery. However, emergency agitation (EA) and emergency delirium (ED), as major complications following sevoflurane anesthesia in children, pose risks to surgery and prognosis. Identifying the high risk of EA/ED, especially anesthesia exposure and the depth of anesthesia, may allow preemptive treatment. Methods: A total of 137 patients were prospectively enrolled in this single-center observational cohort study to assess the incidence of EA or ED. Multivariable logistic regression analyses were used to test the association between volatile anesthesia exposure and depth with EA or ED. The Richmond Agitation and Sedation Scale (RASS), Pediatric Anesthesia Emergence Delirium Scale (PAED) and Face, Legs, Activity, Cry, and Consolability (FLACC) behavioural pain scale was used to assess the severity of EA or ED severity and pain. Bispectral index (BIS) to monitor the depth of anesthesia, as well as TimeLOW-BIS/TimeANES %, EtSevo (%) and EtSevo-time AUC were included in the multivariate logistic regression model as independent variables to analyze their association with EA or ED. Results: The overall prevalence of EA and ED was 73/137 (53.3%) and 75/137 (54.7%) respectively, where 48/137 (35.0%), 19/137 (13.9%), and 6/137 (4.4%) had mild, moderate, and severe EA. When the recovery period was lengthened, the prevalence of ED and extent of FLACC decreased and finally normalized within 30 min in recovered period. Multivariable logistic regression demonstrated that intraoperative agitation [2.84 (1.08, 7.47) p = 0.034], peak FLACC [2.56 (1.70, 3.85) p < 0.001] and adverse event (respiratory complications) [0.03 (0.00, 0.29) p = 0.003] were independently associated with higher odds of EA. Taking EtSevo-time AUC ≤ 2,000 as a reference, the incidence of EA were [15.84 (2.15, 116.98) p = 0.002] times and 16.59 (2.42, 113.83) p = 0.009] times for EtSevo-time AUC 2,500-3,000 and EtSevo-time AUC > 3,000, respectively. Peak FLACC [3.46 (2.13, 5.62) p < 0.001] and intraoperative agitation [5.61 (1.99, 15.86) p = 0.001] were independently associated with higher odds of developing ED. EtSevo (%), intraoperative BIS value and the percentage of the duration of anesthesia at different depths of anesthesia (BIS ≤ 40, BIS ≤ 30, BIS ≤ 20) were not associated with EA and ED. Conclusions: For pediatrics undergoing ambulatory surgery where sevoflurane anesthesia was administered, EA was associated with surgical time, peak FLACC, respiratory complications, and "EtSevo-time AUC" with a dose-response relationship; ED was associated with peak FLACC and intraoperative agitation.

NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2.

Postoperative cognitive dysfunction (POCD) is a common complication of cognitive decline after surgery and anesthesia. Sevoflurane, as a commonly used anesthetic, was found to cause POCD. Nudix Hydrolase 21 (NUDT21), a conserved splicing factor, has been reported to exert important functions in multiple diseases' progression. In this study, the effect of NUDT21 on sevoflurane-induced POCD was elucidated. Results showed that NUDT21 was down-regulated in the hippocampal tissue of sevoflurane-induced rats. Morris water maze test results revealed that overexpression of NUDT21 improved sevoflurane-induced cognitive impairment. In addition, TUNEL assay results indicated that enhanced NUDT21 alleviated sevoflurane-induced apoptosis of hippocampal neurons. Furthermore, overexpression of NUDT21 suppressed the sevoflurane-induced LIMK2 expression. Taken together, NUDT21 alleviates sevoflurane-induced neurological damage in rats by down-regulating LIMK2, providing a novel target for the prevention of sevoflurane-induced POCD.

Individualized red-cell transfusion strategy for non-cardiac surgery in adults: a randomized controlled trial.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01597232.

Activation of autophagy inhibits the activation of NLRP3 inflammasome and alleviates sevoflurane-induced cognitive dysfunction in elderly rats.

AIMS/INTRODUCTION: As a common complication in elderly patients after surgery/anesthesia, postoperative cognitive dysfunction (POCD) is mainly characterized by memory, attention, motor, and intellectual retardation. Neuroinflammation is one of the most uncontroversial views in POCD. The sevoflurane-induced neurotoxicity has attracted widespread attention in recent years. However, its mechanism has not been determined. This study aimed to observe the effects of sevoflurane on cognitive function and the changes in inflammatory indices and autophagy protein expression in the prefrontal cortex in aged rats. METHOD: Before the experiment, D-galactose was diluted with normal saline into a liquid with a concentration of 125 mg/kg and injected subcutaneously into the neck and back of rats for 42 days to establish the aging rat model. Morris water maze experiments were performed, including positioning navigation (5 days) and space exploration (1 day). The POCD model was established by 3.2% sevoflurane inhalation. The rats were treated with or without MCC950, a potent and selective nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inhibitor, followed by autophagy agonists and autophagy inhibitors. The expression levels of inflammasome-related protein NLRP3 and autophagy-related proteins LC3B and P62 were detected to test the behavior of rats with a water maze. RESULTS: We found that sevoflurane exposure affected learning and working memory ability in aged rats. We also observed microglia activation in the prefrontal cortex. NLRP3 protein expression was significantly upregulated after sevoflurane inhalation. NLRP3 inflammasome activation induced increased expression and mRNA expression of cleaved Caspase-1 and inflammatory cytokines IL-1ß and IL-18, and increased secretion of peripheral proinflammatory cytokines. The inhibitor MCC950 was used to improve cognitive ability and inflammation in rats and inhibit the secretion of cytokines. In addition, we demonstrated that significant inhibition of autophagy (decreased LC3-II/I and increased P62) was accompanied by increased activation of NLRP3 inflammasomes and more severe neural cell damage. However, autophagy inhibitor rapamycin administration to activate autophagy resulted in the inhibition of NLRP3 inflammasomes, ultimately attenuating neuronal injury. CONCLUSIONS: The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.

Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age.

BACKGROUND: The aim of the study was to determine the effects of repeated anesthesia exposure across postnatal development. METHODS: Seventy-two newborn Sprague-Dawley rats were randomly divided into Sev group and Con-aged group. Sev groups were exposed to 2.6% sevoflurane for 2 h on postnatal day (P) 7, P14, and P21; the Con groups only received carrier gas for 2 h. Learning and memory were evaluated using the MWM test at P31 (juvenile), P91 (adult), and 18 months postnatally (aged). The relative expression of APP and Mapt mRNA was detected by RT-PCR, while Aß, tau, and P-tau protein levels were analyzed by immunohistochemistry. RESULTS: After repeated inhalation of sevoflurane, MWM test performance was significantly decreased in the Sev-aged group compared to the Con-aged group (P > 0.05). The relative expression of APP and Mapt mRNA was not significantly different between groups in each growth period (P > 0.05). The tau expression in the juvenile hippocampal CA1, CA3, and dentate gyrus regions increased markedly in the Sev group, while P-tau only increased in the hippocampal CA3 region in the Sev-adult group. The expression of tau, P-tau, and Aß in the hippocampal regions was upregulated in the Sev-aged group. CONCLUSIONS: Multiple exposures to sevoflurane across postnatal development can induce or aggravate cognitive impairment in old age. IMPACT: Whether multiple sevoflurane exposures across postnatal development cause cognitive impairment in childhood, adulthood, or old age, as well as the relationship between sevoflurane and the hippocampal Aß, tau, and P-tau proteins, remains unknown. This study's results demonstrate that multiple exposures to sevoflurane across postnatal development do not appear to affect cognitive function in childhood and adulthood; however, multiple exposures may lead to a cognitive function deficit in old age. The underlying mechanism may involve overexpression of the tau, P-tau, and Aß proteins in the hippocampus.

Progress in the correlation of postoperative cognitive dysfunction and Alzheimer's disease and the potential therapeutic drug exploration.

Postoperative cognitive dysfunction (POCD) is a decrease in mental capacity that can occur days to weeks after a medical procedure and may become permanent and rarely lasts for a longer period of time. With the continuous development of research, various viewpoints in academic circles have undergone subtle changes, and the role of anesthesia depth and anesthesia type seems to be gradually weakened; Alzheimer's disease (AD) is a latent and progressive neurodegenerative disease in the elderly. The protein hypothesis and the synaptic hypothesis are well-known reasons. These changes will also lead to the occurrence of an inflammatory cascade. The exact etiology and pathogenesis need to be studied. The reasonable biological mechanism affecting brain protein deposition, neuroinflammation, and acetylcholine-like effect has a certain relationship between AD and POCD. Whereas there is still further uncertainty about the mechanism and treatment, and it is elusive whether POCD is a link in the continuous progress of AD or a separate entity, which has doubts about the diagnosis and treatment of the disease. Therefore, this review is based on the current common clinical characteristics of AD and POCD, and pathophysiological research, to search for their common points and explore the direction and new strategies for future treatment.

Gastrodin improves neuroinflammation-induced cognitive dysfunction in rats by regulating NLRP3 inflammasome.

Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin's effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial.

This current phase II clinical trial was to compare the effect and safety of adamgammadex, a new cyclodextrin-based selective relaxant binding agent, with sugammadex to reverse rocuronium-induced neuromuscular block. Patients were randomised to receive adamgammadex (4 or 6 mg kg-1) or sugammadex (2 mg kg-1, as a positive control group) at the reappearance of the second twitch (T2) in response to TOF stimulation. The standard safety data were collected. The 4 mg kg-1 (n = 16) and 6 mg kg-1 (n = 20) adamgammadex- and 2 mg kg-1 (n = 20) sugammadex-induced recovery time of TOF ratio to 0.9 were 2.3, 1.6, and 1.5 min, respectively (p = 0.49). The 4 mg kg -1 adamgammadex-induced median recovery time was longer than that of 2 mg kg-1 sugammadex (p = 0.01), and there was no difference between the 6 mg kg -1 adamgammadex group and 2 mg kg-1 sugammadex group (p = 0.32). Then, the number of patients who experienced adverse events (AEs) was 6, 11, and 14 for adamgammadex at 4, 6 mg kg-1 and sugammadex at 2 mg kg-1, respectively. The treatment emergent AEs that occurred more than twice were detailed as follows: incision site pain, hypotension, emesis, fever, throat pain, blood bilirubin increase, abnormal T-wave of ECG, dizziness, incision site swelling, postoperative fever, expectoration, and nausea. For drug-related AEs, the increased urine acetone bodies and first-degree atrioventricular block were observed in two patients from sugammadex group. Then, the previously reported AEs were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversal of rocuronium-induced neuromuscular block as sugammadex.